Impact of SIRPα genotype combinations in recipients and donors on alloimmune response in liver transplantation

TL;DR

This study shows that SIRPα genetic variations affect immune responses in liver transplants, with the V2 variant increasing the risk of rejection.

Contribution

The study identifies SIRPα V2 as a novel genetic factor influencing T cell activation and acute rejection in liver transplantation.

Findings

SIRPα V2 has higher CD47 binding and enhances T cell proliferation compared to V1.

SIRPα V2 is associated with increased acute rejection rates in liver transplant recipients.

SIRPα polymorphisms modulate both innate and adaptive immune responses in transplantation.

Abstract

The signal regulatory protein alpha (SIRPα)–CD47 axis regulates self-tolerance by delivering inhibitory signals to phagocytic cells and influencing immune responses in transplantation. This study examined the impact of SIRPα polymorphisms on CD47 binding capacity and T cell activation and analyzed the role of SIRPα genotypes in acute rejection following allogeneic liver transplantation. Peripheral blood mononuclear cells from healthy volunteers and data from liver transplant recipients were analyzed. Results showed that V2 SIRPα exhibited significantly higher CD47 binding capacity and enhanced costimulatory activity on CD4+ T cell proliferation compared V1 under both CD28− and CD28+ conditions, with further augmentation in the CD28+ setting. In the liver transplant cohort, SIRPα V2 was associated with higher acute rejection incidences than V1. These findings suggest that SIRPα polymorphisms, particularly V2, enhance T cell activation and modulate alloimmune responses through both innate and adaptive immunity, with potential implications for transplant outcomes. SIRPα genotyping may serve as one component within broader, multiparameter risk models for acute rejection and help inform optimization of immunosuppressive strategies.

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